Results from the Survey of Antibiotic Resistance (SOAR) 2011–13 in Ukraine

Objectives: To determine the antibiotic susceptibility of respiratory isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2011–13 from Ukraine. Methods: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Results: A total of 134 isolates of S. pneumoniae and 67 of H. influenzae were collected from eight sites in Ukraine. Overall, 87.3% of S. pneumoniae were penicillin susceptible by CLSI oral breakpoints and 99.3% by CLSI iv breakpoints. Susceptibility to amoxicillin/clavulanic acid (amoxicillin), ceftriaxone and levofloxacin was 100% by CLSI and PK/PD breakpoints. Cephalosporin and macrolide susceptibility was ≥95.5% and 88.1%, respectively using CLSI breakpoints. Trimethoprim/sulfamethoxazole was essentially inactive against pneumococci. Of the 67 H. influenzae tested, 4.5% were b-lactamase positive and all H. influenzae were fully susceptible to amoxicillin/ clavulanic acid, ceftriaxone, ciprofloxacin, cefixime and levofloxacin (all breakpoints). Cefuroxime susceptibility was 100% by CLSI but 73.1% by EUCAST and PK/PD breakpoints. A discrepancy was found in macrolide susceptibility between CLSI (100% susceptible), EUCAST (22%–43% susceptible) and PK/PD (0%–22% susceptible) breakpoints. Trimethoprim/sulfamethoxazole was poorly active (59.7% susceptible). Conclusions: Generally, antibiotic resistance was low in respiratory pathogens from Ukraine. However, only amoxicillin/clavulanic acid (amoxicillin), ceftriaxone and levofloxacin were fully active against both species. Trimethoprim/sulfamethoxazole was the least active, particularly against S. pneumoniae. Some susceptibility differences were apparent between CLSI, EUCAST and PK/PD breakpoints, especially with macrolides against H. influenzae. These data suggest that further efforts are required to harmonize these international breakpoints. Future studies are warranted to monitor continued low resistance levels in Ukraine compared with other parts of Eastern Europe

Results from the Survey of Antibiotic Resistance (SOAR) 2011–13 in Ukraine

Objectives: To determine the antibiotic susceptibility of respiratory isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2011–13 from Ukraine. Methods: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Results: A total of 134 isolates of S. pneumoniae and 67 of H. influenzae were collected from eight sites in Ukraine. Overall, 87.3% of S. pneumoniae were penicillin susceptible by CLSI oral breakpoints and 99.3% by CLSI iv breakpoints. Susceptibility to amoxicillin/clavulanic acid (amoxicillin), ceftriaxone and levofloxacin was 100% by CLSI and PK/PD breakpoints. Cephalosporin and macrolide susceptibility was ≥95.5% and 88.1%, respectively using CLSI breakpoints. Trimethoprim/sulfamethoxazole was essentially inactive against pneumococci. Of the 67 H. influenzae tested, 4.5% were b-lactamase positive and all H. influenzae were fully susceptible to amoxicillin/ clavulanic acid, ceftriaxone, ciprofloxacin, cefixime and levofloxacin (all breakpoints). Cefuroxime susceptibility was 100% by CLSI but 73.1% by EUCAST and PK/PD breakpoints. A discrepancy was found in macrolide susceptibility between CLSI (100% susceptible), EUCAST (22%–43% susceptible) and PK/PD (0%–22% susceptible) breakpoints. Trimethoprim/sulfamethoxazole was poorly active (59.7% susceptible). Conclusions: Generally, antibiotic resistance was low in respiratory pathogens from Ukraine. However, only amoxicillin/clavulanic acid (amoxicillin), ceftriaxone and levofloxacin were fully active against both species. Trimethoprim/sulfamethoxazole was the least active, particularly against S. pneumoniae. Some susceptibility differences were apparent between CLSI, EUCAST and PK/PD breakpoints, especially with macrolides against H. influenzae. These data suggest that further efforts are required to harmonize these international breakpoints. Future studies are warranted to monitor continued low resistance levels in Ukraine compared with other parts of Eastern Europe

MAGNETIC PROPERTIES OF AS-QUENCHED SOFT MAGNETIC ALLOYS AFTER HEAT TREATMENT IN NITROGEN ATMOSPHERE

This work presents the results of a study of the effect of heat treatment (HT) at 380 °C in a nitrogen atmosphere on the magnetic properties of as-quenched soft magnetic alloys. It is shown that a significant effect of nitrogen was detected on the Fe-B-Si-C alloy samples as a result of HT at 1 hour

Nuclear Polarization of Molecular Hydrogen Recombined on a Non-metallic Surface

The nuclear polarization of $\mathrm{H}_2$ molecules formed by recombination of nuclear polarized H atoms on the surface of a storage cell initially coated with a silicon-based polymer has been measured by using the longitudinal double-spin asymmetry in deep-inelastic positron-proton scattering. The molecules are found to have a substantial nuclear polarization, which is evidence that initially polarized atoms retain their nuclear polarization when absorbed on this type of surfac

Measurement of Angular Distributions and R= sigma_L/sigma_T in Diffractive Electroproduction of rho^0 Mesons

Production and decay angular distributions were extracted from measurements of exclusive electroproduction of the rho^0(770) meson over a range in the virtual photon negative four-momentum squared 0.5< Q^2 <4 GeV^2 and the photon-nucleon invariant mass range 3.8< W <6.5 GeV. The experiment was performed with the HERMES spectrometer, using a longitudinally polarized positron beam and a ^3He gas target internal to the HERA e^{+-} storage ring. The event sample combines rho^0 mesons produced incoherently off individual nucleons and coherently off the nucleus as a whole. The distributions in one production angle and two angles describing the rho^0 -> pi+ pi- decay yielded measurements of eight elements of the spin-density matrix, including one that had not been measured before. The results are consistent with the dominance of helicity-conserving amplitudes and natural parity exchange. The improved precision achieved at 47 GeV, reveals evidence for an energy dependence in the ratio R of the longitudinal to transverse cross sections at constant Q^2.Comment: 15 pages, 15 embedded figures, LaTeX for SVJour(epj) document class Revision: Fig. 15 corrected, recent data added to Figs. 10,12,14,15; minor changes to tex

Abrogation of Cbl–PI3K Interaction Increases Bone Formation and Osteoblast Proliferation

Cbl is an adaptor protein and E3 ligase that plays both positive and negative roles in several signaling pathways that affect various cellular functions. Tyrosine 737 is unique to Cbl and phosphorylated by Src family kinases. Phosphorylated CblY737 creates a binding site for the p85 regulatory subunit of phosphatidylinositol 3 kinase (PI3K) that also plays an important role in the regulation of bone homeostasis. To investigate the role of Cbl–PI3K interaction in bone homeostasis, we examined knock-in mice in which the PI3K binding site on Cbl was ablated due to the substitution of tyrosine 737 to phenylalanine (CblYF/YF, YF mice). We previously reported that bone volume in these mice is increased due to decreased osteoclast function (Adapala et al., J Biol Chem 285:36745–36758, 19). Here, we report that YF mice also have increased bone formation and osteoblast numbers. In ex vivo cultures bone marrow-derived YF osteoblasts showed increased Col1A expression and their proliferation was also significantly augmented. Moreover, proliferation of MC3T3-E1 cells was increased after treatment with conditioned medium generated by culturing YF bone marrow stromal cells. Expression of stromal derived factor-1 (SDF-1) was increased in YF bone marrow stromal cells compared to wild type. Increased immunostaining of SDF-1 and CXCR4 was observed in YF bone marrow stromal cells compared to wild type. Treatment of YF condition medium with neutralizing anti-SDF-1 and anti-CXCR4 antibodies attenuated MC3T3-E1 cell proliferation. Cumulatively, these results show that abrogation of Cbl–PI3K interaction perturbs bone homeostasis, affecting both osteoclast function and osteoblast proliferation

Effectiveness of intravenous isoniazid and ethambutol administration in patients with tuberculosis meningoencephalitis and HIV infection

Effectiveness of intravenous isoniazid and ethambutol administration in patients with tuberculosis meningoencephalitis and HIV infection / Dmytro Butov, Yurii Feshchenko, Mykhailo Kuzhko, Mykola Gumenuik, Kateryna Yurko, Alina Grygorova, Anton Tkachenko, Natalia Nekrasova, Tetiana Tlustova, Vasyl Kikinchuk, Alexandr Peshenko, Tetiana Butova // Tuberculosis and Respiratory Diseases. – 2019. – № 82. – Р. 1-8. – DOI: https://doi.org/10.4046/trd.2019.0021Метою даного дослідження було вивчення ефективності внутрішньовенного введення ізоніазиду (І) та етамбутолу (Е) у пацієнтів з лікарсько-чутливим туберкульозом легень (ТЛ) з позитивним результатом мокротиння, туберкульозним менінгоенцефалітом (ТМ) та вірусом імунодефіциту людини (ВІЛ) у інтенсивній фазі лікеування. При ТЛ/ТМ з ВІЛ внутрішньовенне лікування І та Е було більш ефективним, ніж пероральне лікування І та Е, через 2 місяці інтенсивного лікування в конверсії мокротиння, а також у клінічному поліпшенні, що супроводжується значно вищими середніми концентраціями у сироватці. Крім того, рівень смертності був нижчим при внутрішньовенному лікуванні І та Е порівняно з пероральним лікуванням.The aim of this study was to investigate the effectiveness of intravenous isoniazid (H) and ethambutol (E) administered in patients with new sputum positive drug-susceptible pulmonary tuberculosis (TB) with tuberculous meningoencephalitis (TM) and human immunodeficiency virus (HIV) co-infection in the intensive phase of treatment. In TB/TM with HIV, the intravenous H and E treatment was more effective than oral H and E treatment at 2 months of intensive treatment in sputum conversion as well as in clinical improvement, accompanied by significantly higher mean serum concentrations. In addition, the mortality rate was lower in intravenous H and E treatment compared to oral treatment.Целью данного исследования было изучение эффективности внутривенного введения изониазида (И) и этамбутола (Э) у пациентов с лекарственно-чувствительным туберкулезом легких (ТЛ) с положительным результатом мокроты, туберкулезным менингоэнцефалитом (ТМ) и вирусом иммунодефицита человека (ВИЧ) в интенсивной фазе лечения. При ТЛ/ТМ с ВИЧ внутривенное лечение И и Э было более эффективным, чем пероральное лечение И и Э, через 2 месяца интенсивного лечения в конверсии мокроты, а также в клиническом улучшении, сопровождаемом значительно более высокими средними концентрациями в сыворотке. Кроме того, уровень смертности был ниже при внутривенном лечении И и Э по сравнению с пероральным лечением

Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski, Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy), Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy

SLI-1 Cbl Inhibits the Engulfment of Apoptotic Cells in C. elegans through a Ligase-Independent Function

The engulfment of apoptotic cells is required for normal metazoan development and tissue remodeling. In Caenorhabditis elegans, two parallel and partially redundant conserved pathways act in cell-corpse engulfment. One pathway, which includes the small GTPase CED-10 Rac and the cytoskeletal regulator ABI-1, acts to rearrange the cytoskeleton of the engulfing cell. The CED-10 Rac pathway is also required for proper migration of the distal tip cells (DTCs) during the development of the C. elegans gonad. The second pathway includes the receptor tyrosine kinase CED-1 and might recruit membranes to extend the surface of the engulfing cell. Cbl, the mammalian homolog of the C. elegans E3 ubiquitin ligase and adaptor protein SLI-1, interacts with Rac and Abi2 and modulates the actin cytoskeleton, suggesting it might act in engulfment. Our genetic studies indicate that SLI-1 inhibits apoptotic cell engulfment and DTC migration independently of the CED-10 Rac and CED-1 pathways. We found that the RING finger domain of SLI-1 is not essential to rescue the effects of SLI-1 deletion on cell migration, suggesting that its role in this process is ubiquitin ligase-independent. We propose that SLI-1 opposes the engulfment of apoptotic cells via a previously unidentified pathway.National Cancer Institute (U.S.) (Award K08CA104890

The Ubiquitin/Proteasome System Mediates Entry and Endosomal Trafficking of Kaposi's Sarcoma-Associated Herpesvirus in Endothelial Cells

Ubiquitination, a post-translational modification, mediates diverse cellular functions including endocytic transport of molecules. Kaposi's sarcoma-associated herpesvirus (KSHV), an enveloped herpesvirus, enters endothelial cells primarily through clathrin-mediated endocytosis. Whether ubiquitination and proteasome activity regulates KSHV entry and endocytosis remains unknown. We showed that inhibition of proteasome activity reduced KSHV entry into endothelial cells and intracellular trafficking to nuclei, thus preventing KSHV infection of the cells. Three-dimensional (3-D) analyses revealed accumulation of KSHV particles in a cytoplasmic compartment identified as EEA1+ endosomal vesicles upon proteasome inhibition. KSHV particles are colocalized with ubiquitin-binding proteins epsin and eps15. Furthermore, ubiquitination mediates internalization of both KSHV and one of its receptors integrin β1. KSHV particles are colocalized with activated forms of the E3 ligase c-Cbl. Knock-down of c-Cbl or inhibition of its phosphorylation reduced viral entry and intracellular trafficking, resulting in decreased KSHV infectivity. These results demonstrate that ubiquitination mediates internalization of both KSHV and one of its cognate receptors integrin β1, and identify c-Cbl as a potential E3 ligase that facilitates this process